DNA-Templated Silver Nanocluster/Porphyrin/MnO₂ Platform for Label-Free Intracellular Zn²⁺ Imaging and Fluorescence-/Magnetic Resonance Imaging-Guided Photodynamic Therapy

Developing a theranostic platform that integrates diagnosis and treatment in one single nanostructure is necessary for efficient tumor treatment. Here, we presented a novel theranostic nanoprobe for nonlabeled fluorescence imaging of Zn2+ and 635 nm red light-triggered photodynamic therapy (PDT) by a multifunctional DNA-templated silver nanocluster/porphyrin/MnO2 nanoplatform. MnO2 nanosheets adsorbed hairpin DNA–silver nanoclusters (AgNCs) and porphyrin (P) by facile physisorption, which accelerate the transfection of nanoprobes and P into tumor cells. After entering the cells, the biodegradation of MnO2 nanosheets by glutathione and acidic hydrogen peroxide released AgNCs for label-free Zn2+ fluorescence imaging by the hairpin DNA-fueled dynamic self-assembly of three-way DNA junction architectures, and the released Mn2+ could act as an effective magnetic resonance imaging (MRI) contrast agent. In addition, MnO2 was decomposed in the acidic H2O2-ample environment and produced O2 to overbear hypoxia-related PDT resistance, highly efficient PDT was obtained by excess singlet oxygen (1O2) release of P–AgNCs–MnO2 nanoprobes under light irradiation compared with free P. In vitro and in vivo studies confirmed that P–AgNCs–MnO2 exhibited high fluorescence specificity, excellent PDT effect, and good biocompatibility and could be used as a contrast agent for MRI. This theranostic platform provided a new avenue for the fluorescence and MRI diagnosis of tumors and efficient tumor treatment.